Autoimmune diseases are frequently associated with a reduction in the number and function of regulatory T cells (Tregs). These cells are known to suppress the levels of physiologic auto-reactive T cells. When the levels of auto-reactive T cells are elevated pathological destruction of desirable cells can result. For instance, type 1 diabetes is characterized by T-cell mediated destruction of insulin-producing β-cells.
Dendritic cells (DCs) play a critical role in the maintenance of peripheral tolerance. DCs promote Treg induction, thereby suppressing excessive immune responses. Dendritic cell-based vaccines have been demonstrated to promote tolerance through antigen-presenting cells (APCs). APCs process and present self-peptides in a tolerogenic manner to T-cells, and induce Treg proliferation. Apoptotic cells express surface ligands recognized by APCs via surface molecules such as the phosphatidyl serine (PS) receptor, CD 47, CD 36, and αvβ3. Recent studies imply that these receptors could inhibit DC maturation and induce tolerance.
The present use of dendritic cell-based DCs vaccines, however, suffers from several limitations. For instance, the present approach requires ex-vivo manipulation of patients' cells, which can adversely affect patient safety, and is associated with high cost. In addition, the present dendritic cell-based DCs vaccine compositions have suboptimal ex vivo stability.
Thus, there is a need for developing alternative vaccine compositions that have improved stability and shelf-life. In addition, there is a need for developing vaccine compositions that are effectively delivered to target cells. As will be clear from the disclosure that follows, these and other benefits are provided by the present invention.